title: Phenotypic expression of Hb F in common high Hb F determinants in Thailand: roles of α-thalassemia, 5' δ-globin BCL11A binding region and 3' β-globin enhancer.
abstract: BACKGROUND
  Deletions of δ- and β-globin genes are associated with different Hb F levels. To address this, we have examined hematological and molecular characteristics in a large cohort of high Hb F determinants in Thailand.
  
  
  METHODS
  A total of 160 unrelated adult subjects with heterozygous trait for high Hb F determinants and another 10 patients with compound heterozygous trait for Hb E were selectively recruited. Hematological parameters and Hb analysis were recorded, and α-thalassemia mutations were investigated. DNA deletions causing δβ(0) -thalassemia and hereditary persistence of fetal hemoglobin (HPFH) were identified using multiplex PCR and denaturing high-performance liquid chromatography (HPLC) assays developed.
  
  
  RESULTS
  Four different DNA deletions were detected including the 12.6 kb deletion δβ(0) -thalassemia (n = 79), 79 kb deletion hereditary persistence of fetal Hb (HPFH)-6 (n = 65), Indian deletion-inversion (G) γ((A) γδβ)-thalassemia (n = 15) and 78 kb deletion Chinese (G) γ((A) γδβ)-thalassemia (n = 1). Eighteen cases were found to carry α-thalassemia with 10 different genotypes. All 10 patients who had similar hematological phenotype with that of Hb E-β(0) -thalassemia were found to be compound Hb E-δβ(0) -thalassemia. Differences in hematological features as well as Hb F levels were noted and are presented comparatively.
  
  
  CONCLUSIONS
  Comparison of phenotypes, genotypes, and the deletion breakpoints of these Thai high Hb F determinants indicates that differences in Hb F expression are correlated with the existence of α-thalassemia, the loss of BCL11A binding region located 5' to the δ-globin gene and the 3' β-globin enhancer, which confirms their important roles in fetal Hb expression.
authors.affiliation: The Graduate School, Khon Kaen University, Khon Kaen, Thailand; Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Nattaphol
authors.initials: N
authors.lastname: Prakobkaew
authors.forename: Supan
authors.initials: S
authors.lastname: Fucharoen
authors.forename: Goonnapa
authors.initials: G
authors.lastname: Fuchareon
authors.forename: Nirut
authors.initials: N
authors.lastname: Siriratmanawong
mesh_terms: D000328:Adult; D001665:Binding Sites; D002352:Carrier Proteins / Q000378:metabolism; D004909:Erythrocyte Indices; D005319:Fetal Hemoglobin / Q000737:chemistry / Q000235:genetics*; D023061:Gene Order; D005838:Genotype; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism; D010641:Phenotype; D011485:Protein Binding; D012097:Repressor Proteins; D013785:Thailand; D055542:alpha-Globins / Q000235:genetics; D017085:alpha-Thalassemia / Q000097:blood* / Q000175:diagnosis / Q000235:genetics*; D055544:beta-Globins / Q000235:genetics* / Q000378:metabolism; D017086:beta-Thalassemia / Q000235:genetics; D055546:delta-Globins / Q000235:genetics* / Q000378:metabolism
chemical_list: C486563:BCL11A protein, human; D002352:Carrier Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; D055542:alpha-Globins; D055544:beta-Globins; D055546:delta-Globins; D005319:Fetal Hemoglobin
keywords: BCL11A binding region; Hb F expression; denaturing high-performance liquid chromatography; hereditary persistence of fetal hemoglobin; δβ-thalassemia